Project Summary/Abstract Hispanic/Latino sexual and gender minorities (SGM) are the fastest growing ethnic group of SGM in the U.S. Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among Hispanic/Latinos. SGM inequities in cardiovascular disease (CVD) risk have been identified as early as young adulthood; and minority stress has been identified as a potential moderator. Yet, small numbers of ethnic minority participants in SGM studies have precluded examination of the intersections of sexual orientation, gender identity, and ethnicity. We propose a cost-effective ancillary study that will leverage existing data from the parent Hispanic Community Health Study/Study of Latinos (HCHS/SOL) while collecting new data on sexual orientation, gender identity, stigma, discrimination, stress, coping, social support, and CVD risk. The proposed study is timely because HCHS/SOL participants will be scheduled for their third in-person visits (V3) starting in November 2019. In this study, we will (1) examine the influence of sexual orientation and gender identity on CVD risk among all HCHS/SOL participants at V3 (~9300); (2) model pathways from sexual orientation and gender identity to CVD risk through stigma, discrimination, and stress among a 1:2 matched sub-cohort of SGM and non-SGM participants at V3 (~1680); and (3) examine the influence of stigma/discrimination on sexual orientation and CVD risk relationships among sub-cohort participants at V3. Data analysis will follow a conceptual model derived from the LGBT Minority Stress Model in which excess stigma discrimination against SGM leads to minority stress that increases CVD risk. In this model, coping and social support serve as resilience factors that mitigate the impact of minority stress on CVD risk. Cross-sectional and longitudinal regression models as well as structural equation models will be used to test these relationships. Understanding the influence of stigma-induced stress on CVD risk among Hispanic/Latino SGM has significant implications for the development of culturally-specific CVD risk reduction strategies. Study findings will be used to build on identified Hispanic/Latino cultural strengths to inform adaptation and testing of family and community acceptance interventions. .